Chromosomal study of couples with the history of recurrent spontaneous abortions with diagnosed blightded ovum.

Spontaneous abortion (SAb) is the most common complication of early pregnancy. Numerous risk factors are associated with an increased risk of pregnancy loss such as: Blighted ovum. The aim of this study was to determine the frequency of balanced chromosomal translocations in couples with a history of recurrent spontaneous abortions and ultrasound diagnosed blighted ovum. Sixty Eight couples with the history of spontaneous abortion (diagnosed blighted ovum) were selected and introduced into this survey during 2007-2012 at Medical Genetics department of Mashhad University of Medical Sciences. Giemsa banding technique was used to search for chromosomal balanced translocations. Demographic assessment has not shown any age difference between blighted ovum suffering couples and general population. Consanguineous marriages in blighted ovum suffering couples was significantly higher (P value <0.001) than non-consanguineous marriages (68.5% versus 31.5%), while in general population 62% of were non-consanguineous. The incidences of balanced chromosomal rearrangements as well as the rate of chromosome 9 inversion were 8.3 percent each, in non-consanguineous Blighted ovum suffering couples and the remaining (83.4%) showed normal karyotypes. There was no chromosome 9 inversion in consanguineous blighted ovum suffering couples and the incidence of balanced chromosomal rearrangements was 2.3%. With regard to relatively low incidence of balanced chromosomal rearrangements in consanguineous couples with blighted ovum, it would be reasonable to suggest that single gene determinants may play an important role in such pregnancy complications rather than chromosomal disorders.

pontaneous abortion (SAb), also known as miscarriage, refers to a pregnancy that ends spontaneously before the fetus has reached a viable gestational age (1). SAb is the most common Loss of unrecognized or subclinical pregnancies is even higher, occurring in 13 to 26 percent of all pregnancies (4). Numerous risk factors are associated with an increased risk of pregnancy loss: Age: Advancing maternal age is one of the risk factors for spontaneous miscarriage in healthy women (5). The overall rate of SAb was 11 percent and the approximate frequencies of clinically recognized miscarriage according to maternal age were: age 20 to 30 years (9 to 17 percent), age 35 (20 percent), age 40 (40 percent), and age 45 (80 percent) (6). Previous spontaneous abortion: Past obstetrical history is an important predictor of subsequent pregnancy outcome. The risk of miscarriage in future pregnancy is approximately 24 percent after one miscarriage, 30 percent after two consecutive miscarriages, and 35 percent after three or more consecutive miscarriages (7)(8). By comparison, miscarriage occurred in only 5-10 percent of women in their first pregnancy or in whom the previous pregnancy was successful (7). Gravidity: Some studies have shown an increased risk of miscarriage with increasing gravidity.
Possible reasons for this association include reproductive compensation behavior (pregnancy failure is likely to be associated with repeated attempts at conception resulting in higher gravidity) and short interpregnancy intervals in multigrain (9)(10). Prolonged ovulation to implantation: some studies revealed that prolonged interval (i.e, >10 days) between ovulation and implantation may lead to early fetal loss. Fertilization of older ovum, delayed tubal transport or abnormal uterine receptivity can result to such delays (11)(12). Interval Prolonged time to pregnancy: according to some observational studies, the risk of miscarriage can be increased by prolonged time to achieving pregnancy (13). Maternal weight: Prepregnancy body mass index less than 18.5 or above 25 kg/m 2 has been associated with an increased risk of infertility and SAb (14)(15). Blighted ovum: A blighted ovum is characterized through ultrasound examination by the absence of an embryo in the gestational sac (an embryonic pregnancy) (16).
One-third of the products of conception from spontaneous abortions occurring at or before 8 weeks of gestation are "blighted" or anembryonic.
Blighted or otherwise abnormal embryos may result from chromosomal abnormalities or possible exposure to teratogenes.
Most chromosomal abnormalities in the embryo occur de novo. Rarely, these defects are inherited as a consequence of parental karyotype abnormalities, such as balanced translocations.
Genetic abnormalities will not be detected by conventional cytogenetic analysis (G-banded karyotype) and account for an undefined proportion of spontaneous abortions (17). The aim of this study was to determine the frequency of balanced chromosomal translocations in couples with a history of recurrent spontaneous abortions who were referred to medical cytogenetic laboratory by ultrasound diagnosed blighted ovum.

Materials and Methods
In order to fulfill this study, all couples    (Fig. 1). Furthermore, results from chromosomal investigation on the basis of G-banding technique indicated that, the incidences of balanced chromosomal rearrangements as well as the rate of chromosome 9 inversion were 8.3 percent each, in nonconsanguineous RSA affected couples and the remaining (83.4%) showed apparently normal karyotypes ( Fig. 1 and 3). On the other hand balanced chromosomal rearrangements was detected only in 2.3% of RSA affected couples with consanguineous marriage (Fig. 3).

Discussion
Spontaneous abortion is the most common complication of early pregnancy (1,(18)(19). There is a general consensus that healthy woman should not undergo extensive evaluation after single first trimester or early second trimester spontaneous miscarriage which is a relatively common sporadic event. However, miscarriage occurs in about 10 to 15 percent of clinically recognized pregnancies under 20 weeks of gestation (4,20). It is important to remind that most women with recurrent pregnancy had a good prognosis for eventually having a successful pregnancy even when a definitive diagnosis is not made and no treatment is initiated (5). According to the literature, the prevalence of chromosomal aberrations among couples with repeated spontaneous miscarriages varies in different studies from none to as high as 21.4%. These differences may be related to sample size and to inclusion and exclusion criteria (21)(22).
In the present study, couples presenting recurrent spontaneous abortion at the first trimester  With regard to relatively low incidence of balanced chromosomal rearrangement in consanguineous couples with blighted ovum, it would be reasonable to suggest that a genetic susceptibitty may play an important role in such pregnancy complications rather than chromosomal disorders.